Daily Ards Research Analysis

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a clinically defined, biologically heterogeneous condition with no proven disease-modifying therapies. Retrospective analyses have identified two biologically distinct subphenotypes (hyperinflammatory and hypoinflammatory) of ARDS, with differing outcomes and responses to therapy. Rapid identification of these subphenotypes in an actionable timeframe has previously not been possible. The PHIND study aimed to prospectively identify these subphenotypes and to demonstrate differing 60-day mortality. METHODS: The PHIND study was a prospective, multicentre, observational cohort study conducted in intensive care units (ICUs) within the National Health Service in the UK and the Health Service Executive in Ireland. Adult patients aged 18 years and older with ARDS or acute hypoxaemic respiratory failure (AHRF) were enrolled within 72 h of onset of the syndrome. Eligible patients were required to be receiving invasive mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen. Plasma interleukin (IL-6) and soluble TNF receptor-1 (TNFR1) were quantified at enrolment using a near-patient benchtop immunoanalyser (Randox multiSTAT) with a run time of approximately 1 h. Together with plasma bicarbonate measured from an arterial blood sample, these values were used to prospectively determine subphenotypes on an individual patient basis using a validated parsimonious logistic regression model. The primary outcome was 60-day mortality. The study was registered on ClinicalTrials.gov, NCT04009330. FINDINGS: Between Nov 22, 2019, and Sept 28, 2023, 1853 patients from 30 centres were screened for eligibility. Of these, 1328 were excluded and 525 were recruited into the study, with 512 individuals included. 308 (60%) patients were male, 204 (40%) were female, and mean age was 57·0 years (SD 15·1). 443 (87%) patients were white, 18 (4%) were Black, and 16 (3%) were Asian. 490 were subphenotyped using the near-patient assay: 89 (18%) were classified as hyperinflammatory and 401 (82%) as hypoinflammatory. The primary outcome of 60-day mortality was measured in 486 patients after four patients withdrew consent for confirmation of vital status. 60-day mortality was significantly higher in the hyperinflammatory group (45 [51%] of 88) than in the hypoinflammatory group (111 [28%] of 398; risk ratio 1·8 [95% CI 1·4-2·4], p<0·0001). After adjustment, hyperinflammatory patients had increased odds of 60-day mortality (adjusted odds ratio 2·7 [95% CI 1·6-4·4], p=0·0002). INTERPRETATION: Rapid identification of ARDS inflammatory subphenotypes using a near-patient assay was feasible and associated with many clinical characteristics and outcomes consistent with those described in earlier retrospective studies, including mortality, prevalence of sepsis, and incidence of metabolic acidosis. These findings support the implementation of precision medicine approaches in ARDS and the urgent need for prospective, subphenotype-stratified interventional trials. FUNDING: Innovate UK, Randox Laboratories, and Belfast Health & Social Care Trust.

Oxygen therapy is one of the most widely used interventions in critical care, yet it remains poorly individualized. Recent trials and meta-analysis suggest no mortality difference between conservative and liberal oxygen strategies, reinforcing the perception that dose does not matter within usual ranges. From this perspective, we argue that this apparent neutrality may largely reflect methodological and conceptual limitations, although true clinical equivalence in some patient populations remains plausible and cannot be excluded based on current evidence. Heterogeneous populations, overlapping oxygenation targets, and the absence of exposure metrics (time in hyperoxia, time in hypoxemia, and cumulative partial pressure of arterial oxygen/peripheral oxygen saturation curves) dilute phenotype-specific signals and force distinct physiological responses into a single pooled estimate. We propose a conceptual model in which oxygen behaves as a dose-dependent, time-dependent drug with phenotype-specific therapeutic windows, particularly in chronic hypercapnia, traumatic brain injury, sepsis, and early versus late acute respiratory distress syndrome. Building on this model, we outline a methodological agenda for precision oxygen trials: defining interventions by actual exposure, pre-specifying pathophysiological subgroups, adopting patient-centered core outcome sets, and using adaptive, target-range designs and individual patient data meta-analyses. For contemporary guidelines and research, the key question is no longer whether conservative or liberal oxygen therapy is superior on average, but how to match the right oxygenation range to the right intensive care unit phenotype at the right time. Moving from population-averaged comparisons to exposure-aware, phenotype-oriented strategies is essential if oxygen therapy is to become a truly precision intervention in critical care.

INTRODUCTION: The incidence and microbiological characteristics of coronavirus disease-2019 (COVID-19) associated ventilator-associated pneumonia (VAP) remain a clinical concern. The present study investigates the risk factors associated with VAP and compares the clinical and microbiological characteristics between the patients with and without COVID-19. MATERIALS AND METHODS: This retrospective case-control study was conducted in a tertiary intensive care unit (ICU) between March 2020 and February 2023. Patients with COVID-19 were identified through positive SARS-CoV-2 polymerase chain reactionresults, while non-COVID-19 patients served as controls. Demographic characteristics, comorbidities, clinical parameters, and microbiological data were analyzed. Risk factors for VAP were determined using multivariate logistic regression analysis. The Kaplan-Meier method was used to estimate the cumulative probability of VAP. RESULT: A total of 327 mechanically ventilated patients were enrolled, of whom 154 developed VAP. COVID-19 emerged as an independent predictor of VAP, conferring a 2.47-fold increased risk (p= 0.008). COVID-19 VAP patients had a higher prevalence of acute respiratory distress syndrome (ARDS) (p< 0.001), increased corticosteroid use (p= 0.004) and lower APACHE scores (p< 0.001). Both ICU and hospital case fatality rates were significantly increased in COVID-19 VAP patients. Klebsiella pneumoniae was the predominant pathogen in COVID-19 VAP patients, followed by Acinetobacter baumannii as the second most common pathogen. CONCLUSIONS: COVID-19 is a significant risk factor for VAP, with distinct clinical and microbiological characteristics compared to non-COVID-19 VAP. The greater occurrence of ARDS, corticosteroid use, and multidrug-resistant organisms in COVID-19-associated VAP highlights the urgent need for individualized antimicrobial strategies aimed at reducing infection-related morbidity and mortality.